The activity of the major prostaglandin metabolizing enzymes, 15-hydroxydehydrogenases, is high in blood vessels. However, the enzymes of blood vessels show a preference for PGF2alpha over PGE2, the former being metabolized two to three times faster. These or similar enzymes are also responsible for degrading PGI2 in blood vessels. The major metabolite of PGI2 was identified by thin-layer chromatography as 6,15-diketo-PGF1alpha. These studies on prostaglandin dehydrogenase are directly related to the suggested deficiency of this enzyme activity in the kidneys of a strain of spontaneously hypertensive rats, the New Zealand strain. We have obtained evidence that an endogenous inhibitor of PGDH is found in high concentrations in the kidneys of these rats. This material is heat labile, non-dialyzable, and sensitive to trypsin digestion. An attempt will be made to purify it. As a renal lesion may be primary in the genetically hypertensive rat of the New Zealand strain, we will examine autoregulation of the renal circulation in young rats (16 to 18 weeks old). Preliminary studies suggest that renal autoregulation is impaired in the hypertensive rats when compared to normotensive control rats. Finally, we intend to obtain additional evidence for the degree of coupling of the activities of the renal kallikrein-kinin and prostaglandin systems. Thus, enhancement of the activity of the kallikrein-kinin system should result in increased excretion of prostaglandins and depression of the activity of the kallikrein-kinin system should result in decreased excretion of prostaglandins. These studies will be conducted in unanesthetized rats over a period of several weeks to demonstrate the relationship under more physiological conditions between the renal kallikrein-kinin and prostaglandin systems.